PB2275: TRIAL IN PROGRESS: PHASE 3 TRIAL EVALUATING THE EFFICACY AND SAFETY OF ODRONEXTAMAB PLUS CHEMOTHERAPY VERSUS RITUXIMAB PLUS CHEMOTHERAPY IN PREVIOUSLY UNTREATED FOLLICULAR LYMPHOMA (OLYMPIA-2)
Authors: Silvana Novelli, Ashish Risal, Manjusha Namuduri, Jingxian Cai, Melanie Ufkin, Min Zhu, Sushmita Mukherjee, Jurriaan Brouwer-Visser, Aafia Chaudhry, Hesham Mohamed, Srikanth Ambati, Elżbieta Iskierka-Jażdżewska
Journal: HemaSphere (2023)

Topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical Background: Despite good responses to standard first-line treatment with rituximab (R)-based chemoimmunotherapy (CIT), a proportion of patients with follicular lymphoma (FL) progress within 2 years, resulting in suboptimal long-term outcomes. Additionally, current first-line treatment includes 2 years of rituximab maintenance, which is associated with long-term B-cell depletion. Odronextamab is an off-the-shelf CD20×CD3 bispecific antibody that has shown encouraging efficacy in patients with relapsed/refractory FL, including those who are refractory to or relapsed post rituximab. In the Phase 2 ELM-2 study (NCT03888105), odronextamab demonstrated overall and complete response (CR) rates of 82% and 75%, respectively, median duration of response of 20.5 months, and median progression-free survival (PFS) of 20.2 months, as assessed by independent central review (ICR). With an optimized step-up regimen, odronextamab had a generally manageable safety profile with infrequent treatment-related adverse events leading to treatment discontinuation (7.6%) (Kim, et al. ASH, 2022). These promising results support investigating whether adding odronextamab to chemotherapy improves treatment outcomes compared with R-CIT in the first-line setting and whether fixed duration of odronextamab-chemotherapy offers benefits compared with R-CIT with R maintenance. Aims: To evaluate the efficacy and safety of odronextamab plus chemotherapy with and without odronextamab maintenance versus rituximab plus chemotherapy with rituximab maintenance in patients with previously untreated FL. Methods: OLYMPIA-2 is a Phase 3, open-label, randomized trial of odronextamab plus chemotherapy (Odro-CHOP/Odro-CVP) versus R-CHOP/R-CVP in previously untreated FL. This study consists of Part 1 (safety run-in), followed by Part 2 (randomization) in which patients will be randomized 1:1:1 to receive either Odro-CHOP/Odro-CVP with no maintenance (Arm A), Odro-CHOP/Odro-CVP followed by odronextamab maintenance (Arm B), or R-CHOP/R-CVP followed by rituximab maintenance (Arm C). Odronextamab intravenous infusion is administered 1 week after CHOP/CVP in a step-up regimen to mitigate the risk of cytokine release syndrome. Odro-CHOP/Odro-CVP will be administered for six 21-day cycles. Patients aged ≥18 years with CD20-positive FL (Grade 1–3a, stage II bulky, or stage III/IV), measurable disease, and Eastern Cooperative Oncology Group performance status 0–2 are eligible. Part 1 will enroll patients with Follicular Lymphoma International Prognostic Index 1 (FLIPI 1) score of 3–5. Exclusion criteria include central nervous system lymphoma or leptomeningeal lymphoma and histological evidence of transformation to high-grade or diffuse large B-cell lymphoma. Results: The primary endpoint is CR rate at 30 months (CR30) as assessed by ICR comparing Odro-CHOP/Odro-CVP with maintenance and R-CHOP/R-CVP with maintenance, followed by the comparison of Odro-CHOP/Odro-CVP without maintenance and R-CHOP/R-CVP with maintenance. Key secondary endpoints include PFS (ICR assessed), event-free survival (ICR assessed), investigator-assessed CR30, and patient-reported physical function as measured by change from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC QLQ-C30). An estimated 200 sites globally will participate to enroll 24–48 patients in Part 1 and 669 patients in Part 2. Summary/Conclusion: This Phase 3 trial will determine the utility of odronextamab plus chemotherapy (Odro-CHOP/Odro-CVP) compared with R-CHOP/R-CVP as a first-line treatment for patients with previously untreated FL.Keywords: Follicular lymphoma, Non-Hodgkin’s lymphoma, Phase III, Bispecific